1. Chapter 1 The Genetic Code of Genes and Genomes

2. 1.1 DNA is the molecule of heredity
Inherited traits are determined by the elements of heredity (genes), that are transmitted from parents to offspring in reproduction
Genes are composed of the chemical deoxyribonucleic acid or DNA
Figure 1.6: Molecular structure of a DNA double helix

3. 1.1 DNA is the molecule of heredity
DNA was discovered by Friedrich Miescher in 1869
In 1920s microscopic studies with special stains showed that DNA is present in chromosomes
In 1944 Avery, McLeod, and McCarty provided the first evidence that DNA is the genetic material

4. Avery, McLeod, McCarty Experiment
Avery, McLeod and McCarty identified the chemical substance responsible for changing rough, non-virulent cells of Streptococcus pneumoniae (R) into smooth encapsulated infectious cells (S):
Transforming activity was destroyed by DNAse, not RNAse or protease
Conclusion: transforming factor that converts R cells to S cells is DNA

5. Figure 1.2: Griffith’s experiment demonstrating bacterial transformation

6. Figure 1.3: DNA is the active material in bacterial transformation.

7. Hershey-Chase Experiment
In 1952 Hershey and Chase showed that DNA, not protein, is responsible for phage activity in bacterial cells:
Radioactive phage DNA enters bacteria after attachment, but protein coat of virus remains outside
Phage DNA directs the
reproduction of virus
in infected bacterial cells
Figure 1.5: T2 phages infecting a cell of E. coli
© Oliver Meckes/E.O.S./MPI Tubingen/Photo Researchers, Inc.

8. Figure 1.4: The Hershey–Chase experiment demonstrated that DNA is responsible for directing the reproduction of phage T2

9. 1.2 The Structure of DNA is a double helix composed of two intertwined strands
In 1953 Watson and Crick proposed the three- dimensional structure of DNA
A central feature of double-stranded DNA is complementary base pairing.
DNA is a double-stranded helix comprised of a linear sequence of paired subunits: nucleotides
Each nucleotide contains any one of four bases: adenine, thymine, guanine, and cytosine

10. Figure 1.6: Molecular structure of a DNA double helix

11. DNA structure is a double helix
DNA backbone forms right-handed helix
Each DNA strand has polarity = directionality
The paired strands are oriented in opposite directions = antiparallel
DNA molecule showing the antiparallel
orientation of the complementary strands

12. DNA Replication Watson-Crick model of DNA replication:
The strands of the original (parental) duplex separate
Each parental strand serves as a template for the production of a complementary daughter strand by means of A-T and G-C base pairing

13. Figure 1.7: Replication in a long DNA duplex as originally proposed by Watson and Crick

14. Genes and Proteins
The genetic information contained in the nucleotide sequence of DNA specifies a particular type of protein
Enzymes = proteins that are biological catalysts essential for metabolic activities in the cell
Metabolites = small molecules upon which enzymes act
In 1908 Archibald Garrod proposed that enzyme defects result in inborn errors of metabolism = hereditary diseases

15. Genes and Proteins
Garrod studied alkaptonuria and identified the abnormal excreted substance = homogentisic acid
Alkaptonuria results from a metabolic defect that blocks the conversion of a substrate molecule to a product molecule in a biochemical pathway due to the absence of a required enzyme = metabolic block
In the case of alkaptonuria, a defective homogentisic acid 1,2 dioxygenase is unable to convert homogentisic acid into 4-maleylacetoacetic acid in the pathway for the breakdown of phenylalanine and thyrosine

16. Figure 1.8: Urine from a person with alkaptonuria turns black
Courtesy Daniel De Aguiar

17. Genes and Proteins
Another defective enzyme in the same pathway, phenylalanine hydroxylase (PAH), leads to phenylalanine accumulation which causes the condition known as phenylketonuria (PKU)
Incidence of PKU, characterized by severe mental retardation, is about one in 8000 among Caucasian births.
A defective enzyme results from a mutant gene

18. Figure 1.9: Metabolic pathway for the breakdown of phenylalanine and tyrosine

19. Figure 1.10: Inborn errors of metabolism in the breakdown of phenylalanine and tyrosine

20. Genes and Proteins
In the 1940s George W. Beadle and Edward L. Tatum, using a filamentous fungus Neurospora crassa, demonstrated that each enzyme is encoded in a different gene.
Their experimental approach, now called genetic analysis, led to the one gene–one enzyme hypothesis.

21. Figure 1.11: Beadle and Tatum obtained mutants of the fi lamentous fungus Neurospora crassa

22. Genes and Proteins
Figure 1.12A: Mutant spores can grow in complete medium but not in minimal medium

23. Figure 1.12B: Each new mutant is tested

24. Figure 1.12C: Mutants that can grow on minimal medium supplemented with amino acid are tested

25. Figure 1.12D: Mutants unable to grow in the absence of arginine are tested with likely precursors of arginine

26. Figure 1.13: Metabolic pathway for arginine biosynthesis inferred from genetic analysis of Neurospora mutants

27. Complementation
A mutant screen is a large-scale, systematic experiment designed to isolate multiple new mutations affecting a particular trait
Mutant screens sometimes isolate different mutations in the same gene.
A complementation test brings two mutant genes together in the same cell or organism.

28. The Principal of Complementation
If this cell or organism is nonmutant, the mutations are said to complement one another and it means that mutations are in the different genes.
If the cell or organism is mutant, the mutations fail to complement one another, and it means that mutations are in the same gene.

29. Figure 1.14: Molecular interpretation of a complementation test using heterokaryons

30. Figure 1.15: A method for interpreting the results of complementation tests

31. Complementation
A gene is defined experimentally as a set of mutant alleles that make up one complementation group. Any pair of mutant alleles in such a group fail to complement one another and result in an organism with a mutant phenotype.

32. Central Dogma Central Dogma of molecular genetics: DNA  RNA  Protein
DNA is the informational molecule that does not code for protein directly but rather acts through an RNA intermediate
DNA codes for RNA = transcription
RNA codes for protein = translation

33. Figure 1.16: DNA sequence coding for the first seven amino acids in a polypeptide chain

34. Figure 1.17: The “central dogma” of molecular genetics: DNA codes for RNA, and RNA codes for proteins

35. Figure 1.18: A DNA strand is being transcribed into an RNA strand
Transcription
Transcription is the production of an RNA strand that is complementary in base sequence to a DNA template = messenger RNA (mRNA)
RNA contains the base uracil in place of thymine and the sugar ribose instead of deoxyribose
RNA is synthesized from template DNA following strand separation of the double helix
Figure 1.18: A DNA strand is being transcribed into an RNA strand

36. Base pairing in DNA and RNA
Complementary base pairing specifies the linear sequence of bases in RNA
Adenine pairs with uracil; thymine pairs with adenine; guanine pairs with cytosine

37. Translation
The sequence of bases in mRNA codes for the sequence of amino acids in a polypeptide
The mRNA is translated in a nonoverlapping group of three bases = codons that specify the sequence of amino acids in proteins
Each codon specifies one amino acid
Transfer RNAs (tRNA) contain triplet base sequences = anticodons, which are complementary to codons in mRNA

38. Figure 1.19: mRNA in translation is to carry information contained in a DNA bases to a ribosome

39. Translation
Translation occurs at the ribosomes which contain several types of ribosomal RNA (rRNA)
tRNAs participate in translation by carrying amino acids and positioning them on ribosomes
Translation results in the synthesis of a polypeptide chain composed of a linear sequence of amino acids whose order is specified by the sequence of codons in mRNA

40. Figure 1.16: DNA sequence coding for the first seven amino acids in a polypeptide chain

41. Table 1.1 The Standard Genetic Code

42. Mutations Mutation refers to any heritable change in a gene
The change may be: substitution of one base pair in DNA for a different base pair; deletion or addition of base pairs
Any mutation that causes the insertion of an incorrect amino acid in a protein can impair its function

43. Figure 1.20: The central dogma in action

44. Figure 1.21: The M1V mutant in the PAH gene

45. Figure 1.22: The R408W mutant in the PAH gene

46. Genes and Environment
One gene can affect more than one trait = pleiotropy
Any trait can be affected by more than one gene as well as environment
Most complex traits are affected by multiple genetic and environmental factors
Often several genes are involved in genetic disorders and the severity of a disease may depend upon genetic status and environmental factors

47. Figure 1.23: Cats with white fur and blue eyes have a high risk of being born deaf, a pleiotropic effect
© Medioimages/Alamy Images

48. Evolution
All creatures on Earth share many features of the genetic apparatus and many aspects of metabolism
Groups of related organisms descend from a common ancestor
Evolution occurs whenever a population of organisms with a common ancestry gradually changes in genetic composition over time

49. Figure 1.24: Evolutionary relationships as inferred from similarities in DNA sequence
Courtesy of Andrew J. Roger, Alastair B. Simpson, and Mitchell L. Sogin

50. Evolution The totality of DNA in a single cell = genome
The complete set of proteins encoded in the genome = proteome
Genes or proteins that derive from a common ancestral sequence via gene duplication = paralogs
Genes that share a common ancestral gene via speciation = orthologs
The molecular unity of life is seen in comparisons among genomes and proteomes

51. Table 1.2 Comparisons of Genomes and Proteomes